This Small Business Innovation Research Phase I project will test the feasibility of a new high-throughput mass spectrometry method for screening genetic disorders in newborns. The next major application area for mass spectrometry is likely to be in clinical diagnostics. In the past few years, LC/MS and MS/MS have been shown to be effective screening methods for a host of neonatal disorders. A promising method is based on flow injection analysis (FIA) using electrospray ionization (ESI) coupled to a triple quadrupole MS operating in precursor or neutral loss MS/MS mode. By measuring abnormal ratios for amino acids and acylcarnitines, this method is capable of screening for multiple disorders in as little time as 2 min per sample, However, significant sample preparation is required before analysis. We propose a method that can significantly improve analysis speed, accuracy, and cost per sample, and which potentially requires less sample preparation than the current methods. Our method is based on the use of low-pressure photoionization (LPPI) coupled to a quadrupole ion trap, time-of-flight (QitTof) mass spectrometer(MS). The principal advantages are (i) minimization of ion suppression by LPPI vs ESI, (ii)increased rate of MS/MS analysis by QitTof vs triple quadrupole MS, and (iii) simplification of the sample preparation requirements.